The molecular nature of psychiatric disorders such as schizophrenia and major depression is still unclear. Lipids may play an important role in the understanding of these disorders, as they are the most abundant yet poorly studied components of the human brain. In this work, we present a comparative lipidomic map of the human brain affected by schizophrenia or major depressive disorder. The study involved three groups of donors, 7 donors each, which included schizophrenic and depressive donors as well as healthy controls. The lipid composition of 36 brain regions was evaluated by liquid chromatography coupled with mass-spectrometry. 616 lipids from 22 lipid classes were identified, and two main trends of lipidomic changes were found. First, CL, PG, BMP and CAR were found to be significantly decreased in both disorders. These lipid classes are associated with mitochondria, pointing towards a possible mitochondrial dysfunction. Second, LPC, CE and Cer were significantly increased in major depression but not in schizophrenia, representing neuroinflammation. On the level of brain regions, cortical regions were affected the most in major depression while white matter regions and the frontal cortex were affected in schizophrenia. Regions of the cerebellum, both grey and white matter, were found to be changed in both disorders. The results of our work indicate significant lipidomic differences between two psychiatric disorders in various regions of the brain associated with mitochondrial dysfunction and cortical neuroinflammation. The study was supported by RFBR, project number №22-15-00474.